Immunotherapies use cancer cells themselves for their treatment

New approach to immunotherapy directly out of the cancer cell

In the treatment of cancer physicians put great hope for the so-called immunotherapy, which is intended to target the body's own defenses targeted against the cancer cells. Here, scientists from the National Center for Tumor Diseases (NCT) Heidelberg of the German Cancer Research Center and the University Hospital Heidelberg (UKHD) have now made significant progress. They produced cancer cells with the help of measles viruses bispecific antibody fragments, so-called "BiTEs" (bispecific T cell engagers).

"Therapeutic approaches that make use of body defense become increasingly important in the treatment of cancer"; explain the scientists of the NCT. One of these new methods is the use of the "BiTEs", which connect T cells with the tumor cells and thus trigger the programmed cell death of the cancer cell. Here, the researchers have now developed a method in which cancer cells produce the antibody fragments themselves. Thus, the BiTEs can be formed directly in the tumors, which promises better treatment success with fewer side effects. The researchers published their results in the journal "Clinical Cancer Research".

Immunotherapy with so-called BiTEs could not only significantly improve treatment options in the future, but also in the case of blood cancer. (Image: fotoliaxrender / fotolia.com)

BiTE therapy already available for blood cancer

So far, according to the experts, the bispecific antibody fragments are only successfully used in a few blood cancers and the treatment is sometimes associated with severe side effects. The artificially produced BiTEs consist of the binding regions of two antibodies that "recognize" different target structures, according to the NCT. One of the two binding sites remains the same in all BiTEs and is reserved for the protein CD3, which occurs on the T cells. The second binding region is varied tumor specifically. Thus, the BiTEs ensure that the T cells are directed to the tumor cell and trigger the programmed cell death there.

Threatening serious side effects in the previous therapy

Although effective BTEs are already being used to treat certain forms of leukemia, the antibody fragments have so far not been used against solid tumors such as skin or colon cancer, according to NCT cancer researcher Christine Engeland. In addition, there is the problem that the "BiTEs are administered so far as a continuous infusion" and thereby "serious, sometimes life-threatening side effects occur"; explains the expert.

Modified measles viruses help with BiTE production

Searching for possible approaches to improving BiTE treatment, scientists from the Virotherapy group of Guy Ungerechts at the NCT Heidelberg used attenuated measles viruses, which were modified so that the bispecific antibody fragments were subsequently formed directly in the tumors. In experiments on mice, they were able to show that the modified attenuated measles viruses do not cause disease, but multiply in tumor cells, so that subsequently - through the cancer cells themselves - the BiTEs are produced.

Significantly fewer side effects

"The advantage of this method is that no BiTEs get into the bloodstream and thus side effects are avoided," emphasizes Christine Engeland. According to the scientists, the risk of side effects was very low when using the procedure and no signs of toxicity were found. In addition, the virus proliferation in the tumor stimulate the body's immune system, which makes the defense, so to speak, aware of the cancer.

Even with skin and colon cancer successes

The doctoral students Tobias Speck and Johannes Heidbüchel were also able to show in tests on mice that treatment with BiTE viruses significantly prolonged survival in skin and colon cancer and even caused healing in some animals. The NCT expert Christine Engeland now hopes "that the new therapy concept is an effective strategy in the treatment of tumors in humans." To check this, however, further investigations are required, with which the scientists want to start this year. (Fp)